1. Academic Validation
  2. Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

Reelin Promotes Cisplatin Resistance by Induction of Epithelial-Mesenchymal Transition via p38/GSK3β/Snail Signaling in Non-Small Cell Lung Cancer

  • Med Sci Monit. 2020 Aug 7;26:e925298. doi: 10.12659/MSM.925298.
Ji-Min Li 1 Fang Yang 1 Juan Li 2 Wei-Qi Yuan 1 Hao Wang 1 Yi-Qin Luo 1
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, The Affiliated Anhui Provincial Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
  • 2 Department of Blood Transfusion, The Affiliated Anhui Provincial Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Abstract

BACKGROUND Emerging evidence suggests the involvement of Reelin in chemoresistance in various cancers. However, its function in cisplatin (DDP) sensitivity of non-small cell lung Cancer (NSCLC) needs to be investigated. MATERIAL AND METHODS Reelin expression in cisplatin-sensitive A549 cells and cisplatin-resistant NSCLC (A549/DDP) cells was analyzed by western blot analysis. qRT-PCR, western blotting, immunofluorescence, CCK-8 assays, Annexin V/propidium iodide Apoptosis assay, and Transwell migration assays were carried out to determine the function of Reelin on DDP resistance. RESULTS Reelin was markedly increased in A549/DDP cells relative to A549 cells. Knockdown of Reelin enhanced DDP chemosensitivity of A549/DDP cells, whereas overexpression of Reelin enhanced DDP resistance of A549, H1299, and H460 cells. Reelin induced DDP resistance in NSCLC cells via facilitating epithelial-mesenchymal transition (EMT). Furthermore, Reelin modulated p38/GSK3ß signal transduction and promoted Snail (EMT-associated transcription factor) expression. Suppression of p38/Snail reversed Reelin-induced EMT and resistance of NSCLC cells to DDP. CONCLUSIONS These data indicated that Reelin induces DDP resistance of NSCLC by regulation of the p38/GSK3ß/Snail/EMT signaling pathway and provide evidence that Reelin suppression can be an effective strategy to suppress DDP resistance in NSCLC.

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